Ch. 5: Non-opioid Analgesics

What does tissue damage lead to the production of?

bradykinin

• a key inflammatory mediator

• = pain!

Production of bradykinin stimulates the production of ______.

arachidonic acid

Arachidonic acid is converted to ____ using _____.

prostaglandins; cyclooxygenases (COX-1, COX-2)

What is the function of cyclooxygenase 1 (COX-1)?

maintains homeostatic functions

What is the function of cyclooxygenase 2 (COX-2)?

mediates inflammation

What are the homeostatic effects of prostaglandins?

• renal homeostasis

• gastric mucosal protectioon

• platelet function

*mediated by renal tubule cells, GI mucosal cells, & platelets

What are the inflammatory effects of prostaglandins?

• pain

• inflammation

• fever

• limited homeostatic effects

*mediated by chondrocytes, fibroblasts, endothelial cells, & macrophages

What are the 3 properties of NSAIDs?

• Analgesic = reduces sensation to pain

• Anti-inflammatory = reduces inflammation

• Anti-pyretic = reduces fever

What do NSAIDs inhibit?

cyclooxygenase 1 and 2

NSAID selection is _____.

patient dependent

• pre-existing medical conditions and current meds often dictate NSAID selection

• different people exhibit variable responses to different NSAIDs

• therapeutic and toxicity differences can be influenced by differences in individual pharmacodynamics, pharmacokinetics, and pharmacogenetics

What are the contraindications to NSAIDs?

• Nursing and pregnancy

• Serious bleeding

• Allergy, Asthma, Angioedema

• Impaired renal function

• Drug (anticoagulant)

Inhibition of COX-1 has _____ side effects.

anti-thrombotic - reduces formation of clots

Inhibition of COX-2 has ____ side effects.

pro-thrombotic - increases tendency of forming clots

• can lead to stroke & myocardial infarction

Which NSAID is an irreversible inhibitor of COX-1 and COX-2, enabling anti-platelet activity (anti-COX-1) prophylaxis?

Aspirin

**IRREVERSIBLE! Stops platelets sticking together as easily

Which NSAIDs are reversible inhibitors of COX-1 and COX-2?

Ibuprofen and other propionic acid derivative NSAIDs

how do NSAIDs such as Ibuprofen interfere with the cardioprotective anti-platelet effect of aspirin therapy.

leads to anti-coagulation for just hours, not days like aspirin would do alone

why are The anti-inflammatory benefits of __selective COX-2 inhibitor___ are offset by their higher thrombotic risk.

• COX-2 inhibits platelet aggregation, reducing the formation of clots - when you inhibit this, clots form easier

What is the only FDA-approved selective COX-2 inhibitor in the US?

Celecoxib

• does not inhibit platelets

• useful for pts on Warfarin

Why is acetaminophen unique compared to other NSAIDs?

• it has a CNS versus peripheral mechanism of action

• good for analgesia (pain relief)

• is a poor anti-inflammatory compared to other NSAIDs

What is the drug of choice for treating fever in children?

acetaminophen

• anti-pyretic

Which drug is a good treatment alternative for patients with contraindications to NSAIDs?

acetaminophen

What does acetaminophen overdose cause?

liver cell death via excess production of the toxic metabolite NAPQ1

• depletes protective liver glutathione

• leads to acute liver failure

What are a first line treatment for acute gout?

NSAIDs, such as Indomethacin

• if no contraindications to NSAIDs

Studies suggest that dental pain is most amenable to treatment by _____ and _____.

NSAID analgesics; acetaminophen

What is the NSAID plateau effect?

the maximum alleviation of acute pain occurs at dose between 650-1000mg; above this range, toxic effects become apparent

How does adding acetaminophen to an NSAID to push past the NSAID plateau effect?

provides additive analgesia beyond the plateau effect

• MINIMIZES use of opioids

• acetaminophen (500mg)/ibuprofen (400mg) combo

____ drugs are useful for patients with emotional pain components.

NSAID/opioid combination drugs

What is the downside to using NSAID/opioid combination drugs to provide additive analgesia beyond the plateau effect?

increased risk of opioid side effects:

• nausea

• constipation

• CNS depression/sedation

Depending on patient-specific contraindications, ____ may be better than NSAID/opioid combos for severe pain situations, such as bony impaction surgery.

Ketorolac

Gout is typically treated with ____.

the NSAID Indomethacin

What is Gout treated with if there are contraindications to NSAID use?

Colchicine

PRACTICE EXAM QUESTIONS:

Which of the following enzymes are inhibited by NSAIDs?

a) cyclooxygenase 1

b) calpain 1

c) cyclooxygenase 2

d) cytochrome C reductase

e) both COX-1 and COX-2

e) both COX-1 and COX-2

Which NSAID is an irreversible inhibitor of COX-1 and is used at low doses for anti-platelet prophylaxis?

a) ibuprofen

b) aspirin

c) acetaminophen

d) all of these choices

e) none of these choices

b) aspirin

Mrs. Jennings visits the office to have a cavity filled in one of her molars. After the procedure she comments that she is having jaw pain and asks whether there is something she can take for it. Her past medical history reveals an allergy to pain relievers. You ask her about it and she says that it was an over the counter pain reliever, maybe aspirin but she can't be sure. Based on this information, what pain reliever do you recommend to Mrs. Jennings to minimize her chances of having an allergic reaction?

a) ibuprofen

b) naproxen

c) aspirin

d) acetaminophen

e) diflunisal

d) acetaminophen

Mr. Anderson is a 44 year old recovering heroin addict who has been drug free for 3 years. He comes into the office to have a consultation for a fairly involved oral surgical procedure. In planning his surgery you are concerned about pain management. Given that he is likely to experience moderate to severe pain, a good treatment option, all things considered, would be to plan to administer what drug?

a) aspirin

b) acetaminophen

c) celecoxib

d) ibuprofen/oxycodone (400mg/5mg)

e) ketorolac

e) ketorolac

Which of the following statements is correct?

a) Inhibition of cyclooxygenase 1 has no effect on coagulation.

b) Inhibition of cyclooxygenase 1 tends to promote coagulation.

c) Inhibition of cyclooxygenase 2 tends to inhibit coagulation.

d) Inhibition of cyclooxygenase 2 tends has no effect on coagulation.

e) Inhibition of cyclooxygenase 1 tends to inhibit coagulation, and inhibition of cyclooxygenase 2 tends to promote coagulation.

e) Inhibition of cyclooxygenase 1 tends to inhibit coagulation, and inhibition of cyclooxygenase 2 tends to promote coagulation.

Clinical studies suggest that the most effective mild to moderate pain relief for routine dental procedures is achieved with which of the following drugs?

a) NSAIDs

b) acetaminophen

c) opioids

d) either NSAIDs or acetaminophen

e) either NSAIDs or opioids

d) either NSAIDs or acetaminophen

Your patient's pain is almost, but not completely controlled with maximum doses of the NSAID you prescribed. You suspect an analgesic plateau effect is at work. Which additional drug do you prescribe to overcome the plateau effect and alleviate the pain?

a) aspirin

b) acetaminophen

c) ibuprofen

d) naproxen

e) diflunasil

b) acetaminophen

Which of the medical diagnoses is NOT a contraindication to NSAID use?

a) pregnancy

b) acute renal failure

c) asthma

d) perforated ulcer

e) arthritis

e) arthritis

Ms. Jones is an 80-year-old female. She has arthritis and is on warfarin therapy for congestive heart failure. She is scheduled for a moderately painful dental procedure. You want to be able to treat her post-op pain but minimize exacerbation of her anticoagulated state. Which medication to you choose?

a) aspirin

b) celecoxib

c) diflusanil

d) ketorolac

e) ibuprofen/oxycodone (400mg/5mg)

b) celecoxib

Which of these anti-inflammatory medicines is useful for treating Gout but does not inhibit cyclooxygenase?

a) indomethacin

b) naproxen

c) ketoprofen

d) colchicine

e) aspirin

d) colchicine